Variations in Creatinine Generation Among Patients With Glomerular Disease: Evidence From the NEPTUNE and CureGN Studies
Bibliographic record
Abstract
Rationale & Objective Estimation of glomerular filtration rate (GFR) assumes that creatinine generation (crG) is relatively stable. This study identified factors associated with crG variability and its impact on serum creatinine changes ( Δ Scr) among patients with glomerular disease. Study Design An observational cohort study. Setting & Participants Nephrotic Syndrome Study Network and Cure Glomerulonephropathy adult and pediatric participants with at least one crG measurement. Predictors Potential predictors of crG levels included age, sex, disease diagnosis, weight status, estimated GFR (eGFR), urine protein, steroid use, and nonsteroid immunosuppressant use. crG change ( Δ crG) was then used as an exposure to assess impacts on Δ Scr. Outcomes crG levels and Δ Scr. Analytical Approach The intraclass correlation coefficient illustrated crG variability within individuals. Multivariable linear mixed models identified factors associated with crG levels. Among those with 2+crG measurements, multivariable linear mixed models estimated the association between Δ crG and Δ Scr. Results Among 4,626 crG measurements from 1,081 participants, there was only moderate correlation between measurements within individuals (intraclass correlation coefficient=0.517, 95% CI, 0.482-0.548) overall. For pediatric participants, factors significantly associated with crG included age, sex, weight status, and urine protein. Among adults, significant factors were age, sex, disease diagnosis, weight status, eGFR, steroid use, and nonsteroid immunosuppressant use. Limitations The 24-hour urine collections may have collection error, measured GFR was unavailable, and edema status was unavailable. Conclusions crG was highly dynamic within individuals over time and varied with glomerular disease activity and treatments. The impact of Δ crG on Δ Scr —and subsequently on estimation of kidney function—is potentially large. Accounting for these changes or development of alternative kidney function measures are needed among glomerular disease patients. Plain Language Summary Creatinine generation is often assumed to be stable when using creatinine to estimate kidney function and track kidney function over time, but it can vary with chronic disease. This study showed high variability in creatinine generation within individuals with glomerular disease. Besides age, sex, and weight, important factors that can impact creatinine generation include urine protein in children and kidney function, disease diagnosis, steroid use, and nonsteroid immunosuppressant use in adults. Changes in creatinine generation may also impact changes in the serum creatinine, which would influence estimates of kidney function, but this relationship needs to be studied further. In the meantime, accounting for factors affecting creatinine generation or using alternative estimates of kidney function in patients with glomerular diseases is needed.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.024 | 0.075 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".